Prenatal Ultrasound Diagnosis of Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is a very rare vascular malformation syndrome also referred to as a capillary-lymphatic-venous malformation with unknown aetiology. The aim of our paper is to highlight interesting images, regarding a rare case of foetal Klippel-Trenaunay syndrome diagnosed prenatally in our department and confirmed postnatally with a favourable evolution during the gestation and neonatal periods. This case was diagnosed at 26 weeks gestation and characterised through ultrasound by the presence of superficial multiple cystic structures of different sizes spreading over the left leg with hemihypertrophy and reduced mobility. The cystic lesions were spreading to the left buttock and the pelvic area. The right leg and upper limbs had normal appearance with good mobility. There were no signs of hyperdynamic circulation or foetal anaemia, but mild polyhydramnios was associated. The ultrasound findings were confirmed postnatally, the left leg presented multiple cystic lesions and port wine stains, and there was hypertrophy and fixed position, with favourable evolution at 6 months of life, when the size of the lesions began to decrease and the mobility of the leg improved.

Skeletal Dysplasia: A Case Report.

This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman's first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis-a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy.

A Rare Case of Allantoic Cyst with Patent Urachus in Fetus with a Microdeletion in 1q21.1q21.2 Region.

An allantoic cyst is a rare malformation with a frequency of 3 in 1,000,000 that may be seen antenatally by ultrasound assessment when the connection between the cloaca (future bladder) and the allantois fails to regress. A patent urachus that presents as a cyst (allantoic) is usually considered not to be associated with chromosomal abnormalities, but if it is not repaired after birth this leads to complications such as urinary tract infections and stone formation. We present a case of a fetus diagnosed with allantoic cyst at the first trimester ultrasound assessment at 12 weeks gestation. The follow up scans showed a decrease in size of the allantoic cyst with no other obvious major defects and, when invasive testing (amniocentesis with microarray analysis) was performed, a rare microdeletion, 1q21.1q21.2 was identified (1.82 Mb deletion).

Fetal Surveillance in Pregnancies with Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune condition, that commonly impacts adult women of reproductive age. Myasthenia gravis in pregnancy is rare, but the incidence is higher in different geographical areas. Pregnancies in mothers with MG can have an unfortunate outcome. Acetylcholine receptor antibodies may pass into the fetal circulation and can affect the fetal neuromuscular junction, generating transient MG or even fetal arthrogryposis. The 2016 and 2021 International Consensus Guidance for Management of Myasthenia Gravis issued by Myasthenia Gravis Foundation of America is lacking in recommendation for fetal surveillance for pregnancies in women with MG. The aim of this paper is to highlight fetal and neonatal complications in mothers with MG and to offer antenatal care insights. Close maternal and pregnancy monitoring can improve pregnancy outcome. Patients with MG should be encouraged to conceive, to avoid triggers for exacerbations of the disease during pregnancy and a multidisciplinary team should be established to ensure the optimal support and therapy.

Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia.

BACKGROUND: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat. RESULTS: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78-1.49]; P=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events. CONCLUSIONS: Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Registration: URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.

Screening for Gestational Diabetes during the COVID-19 Pandemic-Current Recommendations and Their Consequences.

Gestational diabetes mellitus (GDM) is recognized as one of the most common medical complications of pregnancy that can lead to significant short-term and long-term risks for the mother and the fetus if not detected early and treated appropriately. Current evidence suggests that, with the use of appropriate screening programs for GDM, those women diagnosed and treated have reduced perinatal morbidity. It has been implied that, when screening for GDM, there should be uniformity in the testing used and in further management. This paper summarizes and compares current screening strategies proposed by international bodies and discusses application in the context of the COVID-19 pandemic.

Prediction of imminent preeclampsia at 35-37 weeks gestation.

BACKGROUND: In the weeks preceding the clinical onset of preeclampsia, the maternal serum level of the angiogenic placental growth factor is decreased and that of the antiangiogenic factor soluble fms-like tyrosine kinase-1 is increased. Women presenting at specialist clinics with signs or symptoms of hypertensive disorders have been stratified according to concentrations of placental growth factor or the ratio of concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor to determine clinical management for the subsequent 1-4 weeks. An alternative approach for the prediction of preeclampsia is use of the competing risks model, a Bayes' theorem based method, to derive patient-specific risk for preeclampsia by various combinations of maternal characteristics and medical history with multiples of the median values of biomarkers. OBJECTIVE: The purpose of this study was to compare the performance of screening for delivery with preeclampsia at ≤2 and ≤4 weeks after assessment at 35+0-36+6 weeks gestation between the use of percentile cut-offs in placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio and the competing risks model. STUDY DESIGN: This was a prospective observational study in women who attended a routine hospital visit at 35+0-36+6 weeks gestation in 2 maternity hospitals in England. The visits included the recording of maternal demographic characteristics and medical history and the measurement of serum placental growth factor and soluble fms-like tyrosine kinase-1 and mean arterial pressure. The areas under the receiver operating characteristics curves were used to compare the predictive performance for preeclampsia with delivery at ≤2 and ≤4 weeks from assessment of screening by placental growth factor alone and the soluble fms-like tyrosine kinase-1/placental growth factor ratio with that of a previously developed competing risks model with a combination of maternal factors, placental growth factor, soluble fms-like tyrosine kinase-1, and mean arterial pressure (triple test). RESULTS: First, the study population of 15,247 pregnancies included 326 pregnancies (2.1%) that subsequently experienced preeclampsia. Second, in the screening for delivery with preeclampsia at ≤2 and ≤4 weeks from assessment, the performance of the triple test was superior to that of placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio. The area under the receiver operating characteristics curves for preeclampsia at ≤2 weeks in screening by the triple test (0.975; 95% confidence interval, 0.964-0.985) was higher than that of placental growth factor alone (0.900; 95% confidence interval, 0.866-0.935; P<.0001) and the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.932; 95% confidence interval, 0.904-0.960; P=.0001). Similarly, the areas under the receiver operating characteristics curves for preeclampsia at ≤4 weeks in screening by the triple test (0.907; 95% confidence interval, 0.886-0.928) was higher than that of placental growth factor alone (0.827; 95% confidence interval, 0.800-0.854; P<.0001) or the soluble fms-like tyrosine kinase-1/placental growth factor ratio (0.857; 95% confidence interval, 0.830-0.883; P<.0001). Third, at most, screen-positive rates of 2-30% the detection rate of delivery with preeclampsia at ≤2 and ≤4 weeks that was achieved by the triple test was approximately 10% higher than that of the soluble fms-like tyrosine kinase-1/placental growth factor ratio and 20% higher than that of placental growth factor alone; the negative predictive value was similar for the 3 tests. CONCLUSION: At 35+0-36+6 weeks gestation, the performance of screening for imminent delivery with preeclampsia by the competing risks model is superior to that of placental growth factor alone or the soluble fms-like tyrosine kinase-1/placental growth factor ratio.

Prediction of small for gestational age neonates: screening by maternal factors, fetal biometry, and biomarkers at 35-37 weeks' gestation.

BACKGROUND: Small for gestational age (SGA) neonates are at increased risk for perinatal mortality and morbidity; however, the risks can be substantially reduced if the condition is identified prenatally, because in such cases close monitoring and appropriate timing of delivery and prompt neonatal care can be undertaken. The traditional approach of identifying pregnancies with SGA fetuses is maternal abdominal palpation and serial measurements of symphysial-fundal height, but the detection rate of this approach is less than 30%. A higher performance of screening for SGA is achieved by sonographic fetal biometry during the third trimester; screening at 30-34 weeks' gestation identifies about 80% of SGA neonates delivering preterm but only 50% of those delivering at term, at a screen-positive rate of 10%. There is some evidence that routine ultrasound examination at 36 weeks' gestation is more effective than that at 32 weeks in predicting birth of SGA neonates. OBJECTIVE: To investigate the potential value of maternal characteristics and medical history, sonographically estimated fetal weight (EFW) and biomarkers of impaired placentation at 35+0- 36+6 weeks' gestation in the prediction of delivery of SGA neonates. MATERIALS AND METHODS: A dataset of 19,209 singleton pregnancies undergoing screening at 35+0-36+6 weeks' gestation was divided into a training set and a validation set. The training dataset was used to develop models from multivariable logistic regression analysis to determine whether the addition of uterine artery pulsatility index (UtA-PI), umbilical artery PI (UA-PI), fetal middle cerebral artery PI (MCA-PI), maternal serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT) would improve the performance of maternal factors and EFW in the prediction of delivery of SGA neonates. The models were then tested in the validation dataset to assess performance of screening. RESULTS: First, in the training dataset, in the SGA group, compared to those with birthweight in ≥10th percentile, the median multiple of the median (MoM) values of PlGF and MCA-PI were reduced, whereas UtA-PI, UA-PI, and sFLT were increased. Second, multivariable regression analysis demonstrated that in the prediction of SGA in <10th percentile there were significant contributions from maternal factors, EFW Z-score, UtA-PI MoM, MCA-PI MoM, and PlGF MoM. Third, in the validation dataset, prediction of 90% of SGA neonates delivering within 2 weeks of assessment was achieved by a screen-positive rate of 67% (95% confidence interval [CI], 64-70%) in screening by maternal factors, 23% (95% CI, 20-26%) by maternal factors, and EFW and 21% (95% CI, 19-24%) by the addition of biomarkers. Fourth, prediction of 90% of SGA neonates delivering at any stage after assessment was achieved by a screen-positive rate of 66% (95% CI, 65-67%) in screening by maternal factors, 32% (95% CI, 31-33%) by maternal factors and EFW and 30% (95% CI, 29-31%) by the addition of biomarkers. CONCLUSION: The addition of biomarkers of impaired placentation only marginally improves the predictive performance for delivery of SGA neonates achieved by maternal factors and fetal biometry at 35+0-36+6 weeks' gestation.

The Impact of 2-(18) Fluoro-2-Deoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in Treatment Strategy of Hodgkin Lymphoma-Current Hematologic Concepts.

Positron emission tomography/computed tomography (PET/CT) is useful in staging of Hodgkin lymphoma (HL), for early response - adapted therapy and choosing an individualized therapy, and is useful in determination of disease extent in relapsed and refractory Hodgkin lymphoma. Interim PET using 2-(18) fluoro-2-deoxyglucose(FDG) and low dose CT performed in one scanning session (FDG-PET/ CT) helps to predict outcome in Hodgkin lymphoma and to asses therapeutic stratification.

Indolent lymphoma: diagnosis and prognosis in medical practice.

INTRODUCTION: Non-Hodgkin lymphomas represent malignant tumors of lymphoid cells. These chronic lymphoproliferative disorders stand for malignancies with varied histological aspects, clinical features, evolution, prognosis and aggressiveness. Follicular lymphomas are the most frequent form of indolent lymphomas and they represent around 25% of all malignant lymphomas in adults. MATERIAL AND METHOD: Between 2011 and 2012, we have retrospectively observed, analyzed and described a group of 24 patients diagnosed with follicular lymphomas in the Department of Hematology from Coltea Hospital. The admittance criteria were: age, gender, hemoglobin and LDH levels, number lymph nodes affected and the Ann Arbor lymphoma staging system. Also used as patient study parameters were the following immunohistochemical criteria: CD20, UCHL1, CD79a, expression of Bcl 2 and Bcl 6, CD10 and the proliferative index (Ki-67). RESULTS: Multiple studies have shown that prognosis depends far more on clinical and histology parameters, including age, the presence of extra-node diseases and the performance status. In our study, regarding the ratio between the two genders, the male patients were more numerous than the female patients. The impairment of the male patients is associated with an unfavorable prognosis. From the age perspective, most of the diagnosed patients were part of the age group over 60. The age exceeding 60 is considered a negative prognosis factor. The serum lactate dehydrogenase (LDH) level is also considered an unfavorable prognosis factor. In our study, stage III and IV were frequently and this represents a poor prognosis factor. CONCLUSIONS: Although it was a small number of patients, the results obtained correspond to the results existing in literature.

Onset risk factors and treatment response features of refractory hodgkin lymphoma.

BACKGROUND: The International Prognostic Factors Project on Advanced Hodgkin lymphoma (HL) developed a seven factor prognostic score consisting of gender, age, stage, serum albumin, hemoglobin, leukocytosis and lymphocytopenia for the newly diagnosed Hodgkin disease patients in advanced stages, who receive chemotherapy. OBJECTIVES: The purpose of this study was to determine whether this prognostic score would also be useful for refractory Hodgkin lymphoma patients in monitoring response to treatment. MATERIAL AND METHOD: In the period 2000-2012, we performed a study on a group of 91 patients to show that the prognostic factors identified by the International Prognostic Factors (IPF) score affect the event- free survival (EFS) and the overall survival (OS). Our study also intends to show that the results of these factors change with the treatment response in patients with HL included in the category of patients with refractory disease. RESULTS: B symptoms, onset lymph node, more than 3 areas involved, bulky disease, extranodal involvement, low serum albumin, erythrocytes sedimentation rate (ESR), C reactive protein (CRP), lactic dehydrogenase (LDH) and anemia were associated with poorer EFS and OS. Male gender, stage, histological type, age (>45 years) and leukocytosis were not associated with significantly poorer outcomes. CONCLUSIONS: the prognostic score for advanced disease is also useful in predicting relapse in patients with HL and early detection of response in patients with refractory HL.

Prognostic factors in myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cell and are characterized by ineffective hematopoiesis with normo- or hyper cellular bone marrow and cytopenia(s).The natural evolution of the disease consists of bone marrow failure (leading to infectious and hemorrhagic episodes or anemia related complications) and transformation to acute myeloid leukemia. Because MDSs display remarkable clinical, pathologic, and cytogenetic heterogeneity, with variable evolution and survival ranging from months to years, the predictive factors of prognosis have a key role in optimal therapeutic decisions.The purpose of this paper is to analyze prognostic factors within a group of patients diagnosed with myelodysplastic syndromes. The prognostic factors taken into account are: the number and depth of cytopenias, percentage of bone marrow blasts, cytogenetic abnormalities, intensity of anemia and transfusional dependence. These factors are related to overall survival, leukemia free survival, bone marrow failure complications, leukemic evolution, treatment decisions and the response to treatment. MATERIAL AND METHOD: The study group comprises of 119 patients diagnosed with de novo MDS, between 2008 and 2011 in the Hematology Department of Coltea Clinical Hospital. In this monitoring period the patients were stratified according to the FAB (French-American-British) morphologic classification. RESULTS: This study revealed that the outcomes of patients with MDS is influenced by the percentage of bone marrow blasts at diagnosis, the number and severity of hematopoietic lineage affected by cytopenia and by the presence of chromosomal abnormalities. CONCLUSIONS: The studied prognostic factors have predictive value in terms of survival, leukemic transformation, treatment response and development of bone marrow failure-related characteristic complications.

Peculiarities in the Diagnosis Approach of MDS /MPN-U Patients.

The most recent WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues describes a set of diseases framed as the MDS / MPN (myelodysplastic / chronic myeloproliferative syndromes). There are four subtypes comprised in this category: chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia and unclassifiable MDS / MPN. They combine both myelodysplastic and myeloproliferative features. Although the unclassifiable MDS/ MPN subtype specifically associates the myelodysplastic and myeloproliferative features, it does not meet the criteria defining the first 3 subtypes. The RARS-T subtype (refractory anemia with ringed sideroblasts associated with marked thrombocytosis) is included in the MDS / MPN-U as a temporary entity. There are two cases described in this article: one diagnosed with RARS-T and one with MDS / MPN-U. Both cases evolved towards acute myeloid leukemia.

Prognostic and predictive significance of the bcl-2/IgH translocation in malignant follicular lymphomas.

BACKGROUND: The t(14;18) translocation, which leads to an overproduction of the bcl-2 protein, supposedly occurs in almost all follicular lymphomas (FL) and can be detected by FISH methods or by PCR. Its detection is useful in monitoring the response to therapy and in assessing minimal residual disease in bone marrow. Recently it was observed that the translocation could become negative after treatment. The prognostic and predictive significance of this fluctuation is not entirely understood. AIM: We intended to find significant correlations among morphological features, histological grades, immunohistochemical findings, and cytogenetical aberrations in malignant follicular lymphomas, in order to identify the prognostic and predictive value of the bcl-2/IgH translocation in these malignancies. MATERIAL AND METHODS: We conducted a study on 79 patients with follicular lymphomas. The study was carried out on tissue samples selected from the "Victor Babes" National Institute of Pathology files. These samples were tested by immunohistochemistry and FISH. RESULTS: Most of the cases (65.2%) were low-grade FL (grade 1-2). Approximately 58.8% of cases in the FISH study group presented t(14;18). In 66.6% of the cases with t(14;18), the immunohistochemical reaction for bcl-2 protein was positive. A significant positive correlation was found between the IHC positivity for bcl-2 and t(14;18) detected by FISH (p=0.04). CONCLUSIONS: Bcl-2 t(14;18) plays an important role in the pathogenesis of follicular lymphoma. FISH is an important tool in the diagnosis, treatment and follow up of these malignancies, since the immunohistochemical testing is negative in a significant proportion of cases.